RESUMO
The X inactive-specific transcript (Xist) gene is the master regulator of X chromosome inactivation in mammals. Xist produces a long noncoding (lnc)RNA that accumulates over the entire length of the chromosome from which it is transcribed, recruiting factors to modify underlying chromatin and silence X-linked genes in cis Recent years have seen significant progress in identifying important functional elements in Xist RNA, their associated RNA-binding proteins (RBPs), and the downstream pathways for chromatin modification and gene silencing. In this review, we summarize progress in understanding both how these pathways function in Xist-mediated silencing and the complex interplay between them.
Assuntos
Proteínas/metabolismo , RNA Longo não Codificante/metabolismo , Inativação do Cromossomo X/genética , Proteínas de Ligação a DNA/metabolismo , Inativação Gênica/fisiologia , Metiltransferases/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptor de Lamina BRESUMO
XIST noncoding RNA promotes the initiation of X chromosome silencing by recruiting the protein SPEN to one X chromosome in female mammals. The SPEN protein is also called SHARP (SMRT and HDAC-associated repressor protein) and MINT (Msx-2 interacting nuclear target) in humans. SPEN recruits N-CoR2 and HDAC3 to initiate histone deacetylation on the X chromosome, leading to the formation of repressive chromatin marks and silencing gene expression. We dissected the contributions of different RNA and protein regions to the formation of a human XIST-SPEN complex in vitro and identified novel sequence and structure determinants that may contribute to X chromosome silencing initiation. Binding of SPEN to XIST RNA requires RRM 4 of the protein, in contrast to the requirement of RRM 3 and RRM 4 for specific binding to SRA RNA. Measurements of SPEN binding to full-length, dimeric, trimeric, or other truncated versions of the A-repeat region revealed that high-affinity binding of XIST to SPEN in vitro requires a minimum of four A-repeat segments. SPEN binding to XIST A-repeat RNA changes the accessibility of the RNA at specific nucleotide sequences, as indicated by changes in RNA reactivity through chemical structure probing. Based on computational modeling, we found that inter-repeat duplexes formed by multiple A-repeats can present an unpaired adenosine in the context of a double-stranded region of RNA. The presence of this specific combination of sequence and structural motifs correlates with high-affinity SPEN binding in vitro. These data provide new information on the molecular basis of the XIST and SPEN interaction.
Assuntos
RNA Longo não Codificante , Proteínas de Ligação a RNA , Feminino , Humanos , Cromatina , Proteínas de Ligação a DNA/genética , Inativação Gênica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Cromossomo X/metabolismo , Inativação do Cromossomo X/genéticaRESUMO
Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.
Assuntos
Transtornos Cromossômicos/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a RNA/genética , Adolescente , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Criança , Pré-Escolar , Deleção Cromossômica , Transtornos Cromossômicos/fisiopatologia , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Haploinsuficiência/genética , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Adulto JovemRESUMO
PURPOSE: Demonstrate the potential of spatiotemporal encoding (SPEN) MRI to deliver largely undistorted 2D, 3D, and diffusion weighted images on a 110 mT portable system. METHODS: SPEN's quadratic phase modulation was used to subsample the low-bandwidth dimension of echo planar acquisitions, delivering alias-free images with an enhanced immunity to image distortions in a laboratory-built, low-field, portable MRI system lacking multiple receivers. RESULTS: Healthy brain images with different SPEN time-bandwidth products and subsampling factors were collected. These compared favorably to EPI acquisitions including topup corrections. Robust 3D and diffusion weighted SPEN images of diagnostic value were demonstrated, with 2.5 mm isotropic resolutions achieved in 3 min scans. This performance took advantage of the low specific absorption rate and relative long TEs associated with low-field MRI. CONCLUSION: SPEN MRI provides a robust and advantageous fast acquisition approach to obtain faithful 3D images and DWI data in low-cost, portable, low-field systems without parallel acceleration.
Assuntos
Encéfalo , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Desenho de Equipamento , Reprodutibilidade dos Testes , Algoritmos , Aumento da Imagem/métodos , Sensibilidade e Especificidade , Análise Espaço-Temporal , Processamento de Sinais Assistido por Computador , Imagem Ecoplanar , Análise de Falha de Equipamento , Interpretação de Imagem Assistida por Computador/métodos , Imagem de Difusão por Ressonância MagnéticaRESUMO
PURPOSE: Central pancreatectomy (CP) offers parenchymal preservation compared to conventional distal pancreato-splenectomy for pancreatic neck and body tumours. However, it is associated with more morbidity. This study is aimed at evaluating the peri-operative and long-term functional outcomes, comparing central and distal pancreatectomies (DPs). METHODS: Retrospective analysis of patients undergoing pancreatic resections for low-grade malignant or benign tumours in pancreatic neck and body was performed (from January 2007 to December 2022). Preoperative imaging was reviewed for all cases, and only patients with uninvolved pancreatic tail, whereby a CP was feasible, were included. Peri-operative outcomes and long-term functional outcomes were compared between CP and DP. RESULTS: One hundred twenty-two (5.2%) patients, amongst the total of 2304 pancreatic resections, underwent central or distal pancreatectomy for low-grade malignant or benign tumours. CP was feasible in 55 cases, of which 23 (42%) actually underwent CP and the remaining 32 (58%) underwent DP. CP group had a significantly longer operative time [370 min (IQR 300-480) versus 300 min (IQR 240-360); p = 0.002]; however, the major morbidity (43.5% versus 37.5%; p = 0.655) and median hospital stay (10 versus 11 days; p = 0.312) were comparable. The long-term endocrine functional outcome was favourable for the CP group [endocrine insufficiency rate was 13.6% in central versus 42.8% in distal (p = 0.046)]. CONCLUSION: Central pancreatectomy offers better long-term endocrine function without any increased morbidity in low malignant potential or benign pancreatic tumours of neck and body region.
Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Estudos Retrospectivos , Fístula Pancreática/cirurgia , Resultado do Tratamento , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/cirurgiaRESUMO
The role of estrogen receptor ß (ERß) in bone health is closely associated with its function in vivo, and ERß-/- mice have been widely utilized to explore the related influences. In this study, ERß-/- female mice were established to investigate the differential expression of circular RNAs (circRNAs) by RNA-Sequencing (RNA-Seq). Among these circRNAs, mmu_circ_0011379 (named Circ-Spen) exhibited high expression in ERß-/- female mice. However, the precise mechanism by which Circ-Spen regulates bone health remained unclear. This study identified Circ-Spen as a positive regulator of mouse bone marrow mesenchymal stem cell (mBMSC) viability. The expression of Circ-Spen was markedly increased in ERß-/- mice femurs tested by RT-qPCR. Moreover, Circ-Spen exhibited an enhanced expression during the bone formation process of mBMSCs. Qualitative experiments also demonstrated that Circ-Spen possessed a circular structure and was localized within the nucleus of mBMSCs. Functionally, it inhibited apoptosis via caspase-3, BCL-2, and BAX, while also promoting autophagy through BECN1 and P62 in mBMSCs tested by MTT assays, transmission electron microscopy (TEM), and Western blotting. These findings reveal the potential of targeting Circ-Spen as a promising therapeutic strategy for rejuvenating senescent mBMSCs and enhancing the efficiency of mBMSC transplantation, which lays the foundation for advancements in the field of bone therapy.
Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Camundongos , Animais , Feminino , RNA Circular/metabolismo , Receptor beta de Estrogênio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Apoptose , Autofagia , MicroRNAs/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
Liver organogenesis is a complex process. Although many signaling pathways and key factors have been identified during liver development, little is known about the regulation of late liver development, especially liver maturation. As a transcriptional repressor, SPEN has been demonstrated to interact with lncRNAs and transcription factors to participate in X chromosome inactivation, neural development, and lymphocyte differentiation. General disruption of SPEN results in embryonic lethality accompanied by hampered liver development in mice. However, the function of SPEN in embryonic liver development has not been reported. In this study, we demonstrate that SPEN is required for hepatocyte maturation using hepatocyte-specific disruption of SPEN with albumin-Cre-mediated knockout. SPEN expression was upregulated in hepatocytes along with liver development in mice. The deletion of the SPEN gene repressed hepatic maturation, mainly by a decrease in hepatic metabolic function and disruption of hepatocyte zonation. Additional experiments revealed that transcription factors which control hepatocyte maturation were strongly downregulated in SPEN-deficient hepatocytes, especially Hnf4α. Furthermore, restoration of Hnf4α levels partially rescued the immature state of hepatocytes caused by SPEN gene deletion. Taken together, these results reveal an unexpected role of SPEN in liver maturation.
Assuntos
Fator 4 Nuclear de Hepatócito , Hepatócitos , Camundongos , Animais , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
PURPOSE: To characterize the mechanism of formation and the removal of aliasing artifacts and edge ghosts in spatiotemporally encoded (SPEN) MRI within a k-space theoretical framework. METHODS: SPEN's quadratic phase modulation can be described in k-space by a convolution matrix whose coefficients derive from Fourier relations. This k-space model allows us to pose SPEN's reconstruction as a deconvolution process from which aliasing and edge ghost artifacts can be quantified by estimating the difference between a full sampling and reconstructions resulting from undersampled SPEN data. RESULTS: Aliasing artifacts in SPEN MRI reconstructions can be traced to image contributions corresponding to high-frequency k-space signals. The k-space picture provides the spatial displacements, phase offsets, and linear amplitude modulations associated to these artifacts, as well as routes to removing these from the reconstruction results. These new ways to estimate the artifact priors were applied to reduce SPEN reconstruction artifacts on simulated, phantom, and human brain MRI data. CONCLUSION: A k-space description of SPEN's reconstruction helps to better understand the signal characteristics of this MRI technique, and to improve the quality of its resulting images.
Assuntos
Algoritmos , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas , Artefatos , Processamento de Imagem Assistida por Computador/métodos , Proteínas de Ligação a DNA , Proteínas de Ligação a RNARESUMO
PURPOSE: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. METHODS: A 2D self-refocused T2 *-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp *Tchirp ) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q Ë 75 encodes with the same off-resonance robustness as EPI. RESULTS: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately Ë85 and Ë108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than Ë1000 ms. CONCLUSION: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning.
Assuntos
Aneurisma , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Marcadores de Spin , Circulação Cerebrovascular , Encéfalo/diagnóstico por imagem , Imagem Ecoplanar/métodos , Campos Magnéticos , Imagem de Perfusão/métodos , Imageamento por Ressonância Magnética , Processamento de Imagem Assistida por Computador/métodosRESUMO
PURPOSE: To assess the feasibility and reliability of a DWI protocol based on spatiotemporally encoding (SPEN), to target prostate lesions along guidelines normally used in EPI-based DWI clinical practice. METHODS: Prostate Imaging-Reporting and Data System recommendations underlying clinical prostate scans were used to develop a SPEN-based DWI protocol, which included a novel, local, low-rank regularization algorithm. These DWI acquisitions were run at 3 T under similar nominal spatial resolutions and diffusion-weighting b-values as used in EPI-based clinical studies. Prostates of 11 patients suspected of clinically significant prostate cancer lesions were therefore scanned using the two methods, with the same number of slices, same slice thickness, and same interslice gaps. RESULTS: Of the 11 patients scanned, SPEN and EPI provided comparable information in 7 of the cases, whereas EPI was deemed superior in a case for which SPEN images had to be acquired with a shorter effective TR owing to scan-time constraints. SPEN provided reduced susceptibility to field-derived distortions in 3 of the cases. CONCLUSIONS: SPEN's ability to provide prostate lesion contrast was most clearly evidenced for DW images acquired with b ≥ 900 s/mm2 . SPEN also succeeded in decreasing occasional image distortions in regions close to the rectum, affected by field inhomogeneities. EPI advantages arose when using short effective TRs, a regime in which SPEN-based DWI was handicapped by its use of nonselective spin inversions, leading to the onset of an additional T1 weighting.
Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos de Viabilidade , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Imagem Ecoplanar/métodosRESUMO
The association between specific genetic mutations and immunotherapy benefits has been widely known, while such studies in pan-cancer are still limited. SPEN, mainly involved in X chromosome inactivation (XCI), plays an essential in tumorigenesis and sex differences in cancer. Thus, we firstly analyzed the potential role of SPEN in the TCGA pan-cancer cohort and clinical samples. Bioinformatics analysis and immunohistochemistry (IHC) staining confirm that the expression of SPEN is significantly different in various cancers and may involve RNA splicing and processing via enrichment analysis. Then, our data further revealed that those patients with SPEN mutation could predict a better prognosis in pan-cancer and had distinct immune signatures, higher tumor mutation burden (TMB), and microsatellite instability (MSI) in common cancer types. Finally, the cancer patients from 9 studies treated with immune checkpoint inhibitors were included to investigate the efficacy of immunotherapy. The results further showed that SPEN mutation was associated with better clinical outcomes (HR, 0.74; 95%CI, 0.59-0.93, P = 0.01), and this association remained existed in female patients (HR, 0.60; 95%CI, 0.38-0.94 P = 0.024), but not in male patients (HR, 0.82; 95%CI, 0.62-1.08 P = 0.150). Our findings demonstrated that SPEN mutation might strongly predict immunotherapy efficacy in pan-cancer.
Assuntos
Neoplasias , Feminino , Humanos , Masculino , Neoplasias/genética , Neoplasias/terapia , Biomarcadores , Carcinogênese , Imunoterapia , Mutação , Proteínas de Ligação a DNA , Proteínas de Ligação a RNARESUMO
Genome-wide association studies identified Spen as a putative modifier of cardiac function, however, the precise function of Spen in the cardiovascular system is not known yet. Here, we analyzed for the first time the in vivo role of Spen in zebrafish and found that targeted Spen inactivation led to progressive impairment of cardiac function in the zebrafish embryo. In addition to diminished cardiac contractile force, Spen-deficient zebrafish embryos developed bradycardia, atrioventricular block and heart chamber fibrillation. Assessment of cardiac-specific transcriptional profiles identified Connexin 43 (Cx43), a cardiac gap junction protein and crucial regulator of cardiomyocyte-to-cardiomyocyte communication, to be significantly diminished in Spen-deficient zebrafish embryos. Similar to the situation in Spen-deficient embryos, Morpholino-mediated knockdown of cx43 in zebrafish resulted in cardiac contractile dysfunction, bradycardia, atrioventricular block and fibrillation of the cardiac chambers. Furthermore, ectopic overexpression of cx43 in Spen deficient embryos led to the reconstitution of cardiac contractile function and suppression of cardiac arrhythmia. Additionally, sensitizing experiments by simultaneously injecting sub-phenotypic concentrations of spen- and cx43-Morpholinos into zebrafish embryos resulted in pathological supra-additive effects. In summary, our findings highlight a crucial role of Spen in controlling cx43 expression and demonstrate the Spen-Cx43 axis to be a vital regulatory cascade that is indispensable for proper heart function in vivo.
Assuntos
Conexina 43/genética , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Fatores de Transcrição/deficiência , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Conexina 43/metabolismo , Modelos Animais de Doenças , Eletrocardiografia , Técnicas de Silenciamento de Genes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/fisiopatologia , Contração Miocárdica/genética , Fenótipo , Transcriptoma , Peixe-ZebraRESUMO
X chromosome inactivation (XCI) is a mammalian-specific process initiated in all female cells, leading to one inactivated X chromosome. The robust nature of XCI, and the complex mechanisms involved in directing this process, makes XCI an important model system to study all aspects of gene regulation. XCI is divided into distinct phases: initiation, establishment, and maintenance of the inactive X (Xi). Recent studies shed important new light on the mechanisms directing all three phases of XCI. These findings include new regulatory pathways in XCI initiation, and the identification of a plethora of new factors involved in establishing and maintaining the Xi. In this review, we will highlight and discuss these new findings in the bigger picture of XCI.
Assuntos
Inativação do Cromossomo X , Animais , Feminino , Humanos , MasculinoRESUMO
PURPOSE: Diffusion MRI is of interest for clinical research and diagnosis. Whereas high- resolution DWI/DTI is hard to achieve by single-shot methods, interleaved acquisitions can deliver these if motion and/or folding artefacts are overcome. Thanks to its ability to provide zoomed, folding-free images, spatially encoded MRI can fulfill these requirements. This is here coupled with a regularized reconstruction and parallel receive methods, to deliver a robust scheme for human DWI/DTI at mm and sub-mm resolutions. METHODS: Each shot along the spatially encoded dimension was reconstructed separately to retrieve per-shot phase maps. These shots, together with coil sensitivities, were combined with spatially encoded quadratic phase-encoding matrices associated to each shot, into single global operators. Their originating images were then iteratively computed aided by l1 and l2 regularization methods. When needed, motion-corrupted shots were discarded and replaced by redundant information arising from parallel imaging. RESULTS: Full-brain DTI experiments at 1 mm and restricted brain DTIs with 0.75 mm nominal in-plane resolutions were acquired and reconstructed successfully by the new scheme. These 3 Tesla spetiotemporally encoded results compared favorably with EPI counterparts based on segmented and selective excitation schemes provided with the scanner. CONCLUSION: A new procedure for achieving high-definition diffusion-based MRI was developed and demonstrated.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Encéfalo/diagnóstico por imagem , HumanosRESUMO
PURPOSE: Spatio-temporal encoding (SPEN) experiments can deliver single-scan MR images without folding complications and with robustness to chemical shift and susceptibility artifacts. Further resolution improvements are shown to arise by relying on multiple receivers, to interpolate the sampled data along the low-bandwidth dimension. The ensuing multiple-sensor interpolation is akin to recently introduced SPEN interleaving procedures, albeit without requiring multiple shots. METHODS: By casting SPEN's spatial rasterization in k-space, it becomes evident that local k-data interpolations enabled by multiple receivers are akin to real-space interleaving of SPEN images. The practical implementation of such a resolution-enhancing procedure becomes similar to those normally used in simultaneous acquisition of spatial harmonics or sensitivity encoding, yet relaxing these methods' fold-over constraints. RESULTS: Experiments validating the theoretical expectations were carried out on phantoms and human volunteers on a 3T scanner. The experiments showed the expected resolution enhancement, at no cost to the sequence's complexity. With the addition of multibanding and stimulated echo procedures, 48-slice full-brain coverage could be recorded free from distortions at submillimeter resolution, in 3 s. CONCLUSIONS: Super-resolved SPEN with SENSE (SUSPENSE) achieves the goals of multishot SPEN interleaving delivering single-shot submillimeter in-plane resolutions in scanners equipped with suitable multiple sensors. Magn Reson Med 79:796-805, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Reprodutibilidade dos TestesRESUMO
PURPOSE: Single-scan two-dimensional MRI has been generally constrained to acquisitions in high quality magnets. This study introduces a methodology, cross-term spatiotemporal encoding (xSPEN), that delivers such images under much poorer external field conditions. METHODS: xSPEN departs from conventional k-space scanning, by relying on spatiotemporally encoding the image being sought. Unlike hitherto proposed SPEN methods, however, xSPEN's image readout does not take place using a field gradient along the direction being probed, but rather with the aid of an ancillary source of inhomogeneous frequency broadening. This ancillary dimension was here imposed by an orthogonal field gradient; for example, images along the "y" axis were read out by application of a "z" gradient. The principles and characteristics of this new approach, compatible with existing scanners and free from the need to collect auxiliary information such as field maps, are presented and discussed. RESULTS: Single- and multi-slice in vitro, ex vivo, and in vivo MRI experiments, confirmed the unusual resilience of this new single-shot MRI method to multiple chemical sites on phantoms, animals and humans. CONCLUSION: xSPEN can deliver single-scan MRI with good sensitivity and exceptional resilience to field inhomogeneities. This could enable investigations that have hitherto escaped from MRI's scope. Magn Reson Med 77:623-634, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Assuntos
Artefatos , Encéfalo/anatomia & histologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Ratos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Spatiotemporal encoding (SPEN) can deliver single-scan MR images without folding complications and with increased robustness to chemical shift and susceptibility artifacts. Yet, it does so at the expense of relatively high specific absorption rates (SAR) owing to its reliance on frequency-swept pulses. This study describes SPEN implementations aimed at full three-dimensional (3D) multislice imaging, possessing reduced SAR thanks to an implementation based on new 2D radiofrequency (RF) pulses. METHODS: Fully refocused spin- and stimulated-echo SPEN sequences incorporating 2D spatial/spatial swept RF pulses were implemented at 3 Tesla and compared to echo planar imaging. The use of effective 90-degree slice-selective excitation pulses enabled the scanning of 3D volumes with a low SAR. RESULTS: Experiments validating the theoretical expectations were carried out on phantoms and on human volunteers, including zooming and diffusion measurements. The chosen sequences showed much smaller SARs than EPI, while delivering similar sensitivities when targeting human brain and fewer distortions when targeting human breast. CONCLUSION: Two-dimensional RF pulses can exploit SPEN's advantages while fulfilling the SAR and multislice coverage demands required for clinical imaging. Magn Reson Med 77:1959-1965, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Assuntos
Encéfalo/diagnóstico por imagem , Mama/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Artefatos , Mapeamento Encefálico , Mama/patologia , Imagem Ecoplanar/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Ondas de RádioRESUMO
PURPOSE: Evaluate the usefulness of single-shot and of interleaved spatiotemporally encoded (SPEN) methods to perform diffusion tensor imaging (DTI) under various preclinical and clinical settings. METHODS: A formalism for analyzing SPEN DTI data is presented, tailored to account for the spatially dependent b-matrix weightings introduced by the sequence's use of swept pulses acting while in the presence of field gradients. Using these b-matrix calculations, SPEN's ability to deliver DTI measurements was tested on phantoms as well as ex vivo and in vivo. In the latter case, DTI involved scans on mice brains and on human lactating breasts. RESULTS: For both ex vivo and in vivo investigations, SPEN data proved less sensitive to distortions arising from Bo field inhomogeneities and from eddy currents, than conventional single-shot alternatives. Further resolution enhancement could be achieved using referenceless methods for interleaved SPEN data acquisitions. CONCLUSION: The robustness of SPEN-based sequences vis-à-vis field instabilities and heterogeneities, enables the implementation of DTI experiments with good sensitivity and resolution even in challenging environments in both preclinical and clinical settings. Magn Reson Med 77:1124-1133, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Assuntos
Encéfalo/anatomia & histologia , Mama/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Algoritmos , Animais , Feminino , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Evaluate the usefulness of diffusion-weighted spatiotemporally encoded (SPEN) methods to obtain apparent diffusion coefficient (ADC) maps of fibroglandular human breast tissue, in the presence of silicone implants. METHODS: Seven healthy volunteers with breast augmentation were scanned at 3 Tesla (T) using customized SPEN sequences yielding separate silicone and water (1) H images in one scan, together with their corresponding diffusion-weightings. RESULTS: SPEN's ability to deliver multiple spectrally resolved images in a single scan, coupled to the method's substantial robustness to magnetic field heterogeneities, served to acquire ADC maps that could be freed from contributions that did not belong to fibroglandular tissue. CONCLUSION: SPEN-based sequences incorporating spectral discrimination and diffusion-weighting enable the acquisition of reliable ADC maps despite the presence of dominant signals from silicone implants, thereby opening new screening possibilities for the identification of malignancies in breast augmented patients.
Assuntos
Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Silicones/química , Adulto , Artefatos , Mama/cirurgia , Implantes de Mama , Feminino , Voluntários Saudáveis , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Campos Magnéticos , Pessoa de Meia-Idade , Modelos Estatísticos , Imagens de Fantasmas , Próteses e Implantes , Água/químicaRESUMO
Our case highlights a rare instance of recurrent metastatic solid pseudopapillary epithelial neoplasms of the pancreas, emerging 8 years after radical pancreatic resection-an extended interval surpassing the reported average. Managing solid pseudopapillary epithelial neoplasm during pregnancy is uniquely challenging, given the increase in the expression of progesterone receptors during the intrapartum period, leading to tumor growth. Although surgical resection remains the primary approach, systemic chemotherapy, radiation therapy, and liver transplant are other considerations. The absence of consensus guidelines for recurrence monitoring emphasizes the need for vigilant, long-term surveillance extending beyond the conventional 5-year mark.